Method for preparing nanoparticles comprising vitamin K and poly-isopropyl-butyl methacrylate-acrylic acid copolymer with supercritical fluid using molecular association theory

Abstract

The present invention relates to a method for preparing supercritical nanoparticles of vitamin K by a supercritical fluid process. The basic concept of the preparation method is as follows. A nanoscaled vitamin K complex is prepared by dissolving vitamin K and a biodegradable polymer in a suitable amount of an organic solvent, spraying the solution into a reactor equilibrated with a supercritical carbon dioxide via a nozzle to obtain particles, introducing supercritical carbon dioxide several times to the particles, extracting the organic solvent out, and then removing carbon dioxide.

1 . A method for preparing a therapeutic agent for skin diseases in the form of nanoparticles comprising vitamin K and a poly-isopropyl-butyl methacrylate-acrylic acid copolymer with a supercritical fluid using a molecular association theory, wherein
 the method comprises the steps of:   dissolving vitamin K and a biodegradable polymer in an organic solvent to prepare a solution (step 1), the proportion of vitamin K is 0.0015 to 0.0018 wt %, the biodegradable polymer is the poly-isopropyl-butyl methacrylate-acrylic acid copolymer, the proportion of the poly-isopropyl-butyl methacrylate-acrylic acid copolymer is 0.0013 to 0.0015 wt %, and ethanol is used as an organic solvent;   spraying the solution into a reactor charged with a supercritical fluid to prepare spherical vitamin K nanoparticles (step 2), carbon dioxide is used as a supercritical fluid, the temperature and the pressure in the reactor are 313.0 to 313.4 K, and 149.5 to 151.3 bars, respectively, the flow rates of carbon dioxide and the solution are 2.5 to 2.7 kg/hr, and 0.47 to 0.50 ml/min, respectively;   introducing a fresh supercritical fluid into the reactor containing the spherical vitamin K nanoparticles to remove the organic solvent (step 3), a back pressure regulator is connected to the outlet to maintain the constant pressure in the reactor by regulating the pressure of the supercritical fluid introduced into the reactor, and the pressure at the outlet is adjusted to 150 bars; and   recovering spherical vitamin K nanoparticles after removal of the organic solvent (step 4).